CN114573457A - Preparation method of malonic half ester - Google Patents

Abstract

The invention discloses a method for preparing a half-ester of malonate. In the presence of a catalyst, the half-ester compound can be obtained by selective hydrolysis of the malonate. Compared with other methods for synthesizing malonic acid half-ester, the selective monohydrolysis reaction of the present invention has simple reaction conditions, mildness and few side reactions. Using a catalyst to promote the monohydrolysis reaction of malonate has high reaction activity and high yield, and has great potential for application.

Description

A kind of preparation method of malonic acid half ester

technical field

The invention relates to a preparation method of a malonic acid half-ester, in particular to the use of nano-zinc oxide as a catalyst for the alkaline hydrolysis reaction of the malonic acid ester to obtain the malonic acid half-ester.

Background technique

Half-ester is a compound with both ester and carboxyl structures on the molecule. It is one of the necessary materials in the synthesis of many important compounds, such as drugs, natural products, polymers, etc. Therefore, the synthesis of half-esters has been subject to many attention of researchers. The synthesis methods of half-esters include ring-opening of cyclic acid anhydrides, monohydrolysis of symmetrical diesters, etc. The ring-opening reaction of the cyclic acid anhydride usually needs to be carried out in a dry anhydrous organic solvent, such as toluene, benzene, ether or chloroform, and the reaction conditions are harsh. Relatively speaking, the single hydrolysis reaction of the symmetrical diester has simple reaction conditions and can be carried out in an aqueous solution, which is more in line with the pursuit of green chemistry. The monohydrolysis reaction of symmetrical diesters is under constant exploration.

Half-ester molecules have two structures of ester group and carboxyl group at the same time, and the different reactivity of ester group and carboxyl group is an important precursor for the construction of many compounds. Monomethyl malonate and monoethyl malonate, which are important intermediates in the synthesis of many drugs and natural products, are the most commonly used half-esters in organic synthesis. esters in higher yields. Compared to other methods for the synthesis of malonic acid half-esters, this selective monohydrolysis reaction is environmentally friendly and simple because it only requires water, a small fraction of volatile co-solvents and inexpensive reagents, and does not require Harmful by-products are produced, so this reaction is of considerable use in chemical synthesis.

SUMMARY OF THE INVENTION

In view of the deficiencies in the prior art, the present invention provides a method for using nano-zinc oxide as a catalyst malonate to carry out an alkaline hydrolysis reaction to obtain a half-ester of malonate.

The specific technical scheme of the present invention is as follows:

A kind of preparation method of malonic acid half ester, its preparation method is as follows:

Specific steps: the malonate reaction substrate is hydrolyzed under the action of a catalyst and a dilute base to obtain a malonate monoester compound.

Further, R in the malonate reaction substrate is C1-C5, preferably R is C1; the catalyst is nano-zinc oxide, the particle size is 10-500 nm, preferably 200 nm; the dilute base is NaOH, LiOH, KOH, One or more of Ca(OH)2, the concentration is 0.1-5.0 mol/L.

Further, the molar ratio of the malonate reaction substrate to the catalyst and the base is 1:0.5%-2%:1-10, preferably 1:1%:2.

Further, the reaction substrate, catalyst and base are heated and refluxed in an organic solvent for reaction.

Further, the reaction time is 3-8 h; the reaction solvent, the organic solvent is one or more of acetone, tetrahydrofuran, and toluene, and the amount of the solvent is 10 times the mass of the malonate reaction substrate.

Further, after the reaction is completed, the solid is separated by filtration, the reaction solution is added with dilute hydrochloric acid to adjust the pH value of the solution to 3, the organic phase is collected by liquid separation, the aqueous phase is extracted with ethyl acetate, and the consumption of ethyl acetate is the same as that of the solvent. The organic phases were combined, and the organic phases were dried over anhydrous magnesium sulfate and then distilled under reduced pressure to obtain the reaction product.

The present invention utilizes a catalyst to promote the monohydrolysis reaction of malonate, has high reaction activity and high yield, and has great application potential.

Detailed ways

The present invention is further described below through specific embodiments, but the present invention is not limited thereto, and the specific protection scope is shown in the claims.

Example 1

10 grams of dimethyl malonate, 1% molar nano-zinc oxide, 2 times the molar amount of alkali solution, 100 grams of organic solvents are added in the reaction flask for heating and refluxing reaction, after the reaction finishes, the solid is filtered and isolated, and the reaction solution adds Dilute hydrochloric acid was used to adjust the pH value of the solution to 3. The reaction solution was extracted with 100 grams of ethyl acetate. The amount of ethyl acetate was the same as that of the solvent. The organic phase was dried over anhydrous magnesium sulfate and then distilled under reduced pressure to obtain the reaction product. The experimental yield was calculated. Rate. In order to obtain the best matching method of various factors and levels, orthogonal experiments were carried out on zinc oxide with different particle sizes of 10-500 nm, different bases (NaOH, LiOH, KOH), different reaction times and different solvents.

Table 1 Orthogonal experiment table

Example 2

Add 10 g of diethyl malonate, 0.5% molar amount of nano-zinc oxide (200 nm), 10 molar amount of LiOH (1 mol/l) alkaline solution, and 100 g of acetone into the reaction flask to heat under reflux for reaction. The solid was separated by filtration, the pH value of the solution was adjusted to 3 by adding dilute hydrochloric acid, the reaction solution was extracted with 100 g of ethyl acetate, the organic phase was dried over anhydrous magnesium sulfate and then distilled under reduced pressure to obtain the reaction product with a yield of 89%.

Example 3

Add 10 grams of dipropyl malonate, 2% moles of nano-zinc oxide (200 nm), 5 moles of LiOH (1 mol/l) alkaline solution, and 100 grams of acetone into the reaction flask to heat under reflux for reaction, the reaction ends After the solid was separated by filtration, dilute hydrochloric acid was added to the reaction solution to adjust the pH value of the solution to 3, the reaction solution was extracted with 100 g of ethyl acetate, the organic phase was dried over anhydrous magnesium sulfate, and then distilled under reduced pressure to obtain the reaction product with a yield of 85%. .

Example 4

Add 10 grams of dipentyl malonate, 2% moles of nano-zinc oxide (200 nm), 2 moles of LiOH (1 mol/l) alkaline solution, and 100 grams of acetone into the reaction flask and heat under reflux for reaction, the reaction ends After the solid was separated by filtration, dilute hydrochloric acid was added to the reaction solution to adjust the pH value of the solution to 3, the reaction solution was extracted with 100 g of ethyl acetate, the organic phase was dried over anhydrous magnesium sulfate, and then distilled under reduced pressure to obtain the reaction product with a yield of 81%. .

Claims (6)

1. The preparation method of the malonic acid half ester is characterized by comprising the following steps:

carrying out hydrolysis reaction on a malonate reaction substrate under the action of a catalyst and dilute alkali to obtain a malonate monoester compound; the reaction equation is as follows:

；

r in the malonate reaction substrate is C1-C5, preferably R is C1; the catalyst is nano zinc oxide with the particle size of 10-500 nm, preferably 200 nm; the dilute alkali is NaOH, LiOH, KOH, Ca (OH)₂The concentration of one or more of (A) is 0.1-5.0 mol/L.

2. The method for preparing half malonate according to claim 1, characterized in that: the molar ratio of the malonate reaction substrate to the catalyst to the base is 1: 0.5% -2%: 1-10.

3. The method for preparing half malonate according to claim 1, characterized in that: the molar ratio of the malonate reaction substrate to the catalyst to the base is 1: 1%: 2.

4. the method for preparing half malonate according to claim 1, characterized in that: heating and refluxing a reaction substrate, a catalyst and alkali in an organic solvent for reaction.

5. The method for preparing half malonate according to claim 4, characterized in that: the reaction time is 3-8 h; the organic solvent is one or more of acetone, tetrahydrofuran and toluene, and the dosage of the solvent is 10 times of the mass of the malonate reaction substrate.

6. The method for preparing half malonate according to claim 1, characterized in that: and after the reaction is finished, filtering and separating out a solid, adding dilute hydrochloric acid into the reaction solution to adjust the pH value of the solution to be 3, separating liquid and collecting an organic phase, extracting a water phase by using ethyl acetate, combining the organic phase, drying the organic phase by using anhydrous magnesium sulfate, and then carrying out reduced pressure distillation to obtain a reaction product.